The maintenance of adequate access to the circulation is critical for the performance of hemodialysis treatment for patients with end-stage renal disease. The three types of vascular access for hemodialysis are the native fistula, the synthetic graft, and the central venous catheter. Native fistulas are the preferred access type because of better long-term patency compared with grafts, and lower rates of infection compared with either grafts or catheters. Unfortunately, a substantial proportion of newly created fistulas (30-55%) are never able to be used for dialysis because of thrombosis within the first few weeks of placement, or vein maturation that is inadequate to support the demands of high-efficiency hemodialysis. In either situation, creation of a new vascular access is usually required. When fistula creation is not feasible due to vessel characteristics, a graft is placed. Although grafts usually function well initially, within one year of placement approximately 50% require intervention to restore adequate function. In the vast majority of cases, graft dysfunction is the result of stenosis formation due to neointimal hyperplasia at the venous outflow. The overall goal of the Dialysis Access Consortium (DAC) is to identify interventions that improve fistula and graft viability. To accomplish this goal the DAC investigators have designed and initiated two multi-center clinical trials. The aim of the Fistula Trial is to determine whether 6-week administration of the anti-platelet drug, clopidogrel, increases the patency rate of newly created fistulas. A secondary aim is to determine whether clopidogrel increases the number of fistulas that are able to be used for dialysis (i.e, the number that mature adequately). The specific aim of the Graft Trial is to determine whether continuous administration of Aggrenox (dipyridamole and low-dose aspirin) prolongs the primary unassisted patency of newly placed grafts. The presumed mechanism of the drug is inhibition of vascular smooth muscle cell proliferation. Monthly measurements of access flow are performed to detect hemodynamically significant stenoses and enable angiographic repair prior to graft thrombosis. Enrollment in these two large, double-blinded, placebo-controlled trials began in January, 2003 and is ongoing. If these drugs are effective, the morbidity, and possibly the mortality, of hemodialysis patients will improve substantially, and the cost of maintaining vascular access should decrease from its current rate of over 1 billion dollars per year.